Potentially inappropriate medications with older people in intensive care and associated factors: a historic cohort study

ABSTRACT BACKGROUND: The epidemiology of potentially inappropriate medications (PIMs) in critical care units remains limited, especially in terms of the factors associated with their use. OBJECTIVE: To estimate the incidence and factors associated with PIMs use in intensive care units. DESIGN AND SETTING: Historical cohort study was conducted in a high-complexity hospital in Brazil. METHODS: A retrospective chart review was conducted on 314 patients aged ≥ 60 years who were admitted to intensive care units (ICUs) at a high-complexity hospital in Brazil. The dates were extracted from a “Patient Safety Project” database. A Chi-square test, Student’s t-test, and multivariable logistic regression analyses were performed to assess which factors were associated with PIMs. The statistical significance was set at 5%. RESULTS: According to Beers’ criteria, 12.8% of the identified drugs were considered inappropriate for the elderly population. The incidence rate of PIMs use was 45.8%. The most frequently used PIMs were metoclopramide, insulin, antipsychotics, non-steroidal anti-inflammatory drugs, and benzodiazepines. Factors associated with PIMs use were the number of medications (odds ratio [OR] = 1.17), length of hospital stay (OR = 1.07), and excessive potential drug interactions (OR = 2.43). CONCLUSIONS: Approximately half of the older adults in ICUs received PIM. Patients taking PIMs had a longer length of stay in the ICU, higher numbers of medications, and higher numbers of potential drug interactions. In ICUs, the use of explicit methods combined with clinical judgment can contribute to the safety and quality of medication prescriptions.


INTRODUCTION
Potentially inappropriate medications (PIMs) are those whose potential risks outweigh their benefits for older people when safer alternative therapeutic options exist. 1 The PIMs use is currently a public health problem worldwide; its magnitude is reflected in epidemiological indicators and negative multidimensional impacts. Rates of PIM use range from 34.6% to 95.8%, depending on the design and other methodological aspects of the studies. [2][3][4][5][6] Use of potentially inappropriate medications is an important predictor of negative outcomes such as falls, deterioration of patients' clinical condition, worsening of pre-existing diseases, higher use of health services, and death. 6,7 In addition to health problems, evidence indicates that using PIM is associated with increased health costs compared to older people who did not use any PIM. 8 There are two methods of assessing the adequacy of drug prescriptions: explicit and implicit.
The implicit method is based on a professional's clinical judgment, considering the clinical particularities of older people; thus, it is more complex and cannot be reproduced or generalized.
At the same time, the explicit method is direct, based on criteria that are usually elaborated upon through expert consensus based on the literature review. 9 Criteria from different countries are used to classify and describe the risks of PIM use, 10,11 so part of these criteria are based on the Beers criterion and local differences regarding the drugs approved for use.
The Beers criteria have been used for over 30 years and are the oldest, even as a risk-management tool. A systematic review identified 36 criteria, with lists of drug classes, drug-disease interactions, and drug-drug interactions, considered educational tools that should be included in the comprehensive assessment of all elderly patients who need medication. 12 Adopting explicit criteria as a way of reviewing the PIM, whether on patient admission or during hospitalization, through computerized systems or not, can help the safe practice of drug prescription for the elderly and reduce the use of PIM in the hospital environment through collaborative work among professionals. 13 The Beers and other criteria should not replace clinical judgment but serve as a guide for the healthcare team in the daily review of medications to minimize the use of PIMs, and to ensure safe and effective pharmacotherapy in the elderly population. 14

OBJECTIVE
The present study was designed to estimate the incidence of and factors associated with the use of potentially inappropriate medications prescribed to older adults in intensive care units.

METHODS
The design was based on the recommendations of the

Data sources and variables
The dates were extracted from a "Patient Safety Project" database. 19  The higher the score, the higher the severity level.

Identification of PIM use
The dependent variable was the regular use of at least one PIM

Statistical analysis
Statistical analyses were performed using SPSS software (ver- To obtain the final model, the adjusted coefficients were presented with 95% confidence intervals. The statistical significance was set at 5%.

Ethical aspects
This study was approved by the local Committee for Ethics in

Profile of the drug therapy regimens of the sample
During the study period, 314 elderly individuals were included for a total of 2,158 days, and 24,938 medications were prescribed.

Older people exposed to PIMs
Approximately half (45.8%) of the older adults (n = 314) were exposed to PIMs. Among them, 59.6% received two to four PIMs, and 29.8% received more than five PIMs. Table 1 presents the sample profiles. Age group, ICU type, polypharmacy, mechanical ventilation, and potential drug interactions were significantly associated (P < 0.05).
Patients taking PIMs had longer lengths of stay in the ICU (P = 0.008), higher numbers of medications (P < 0.001), and higher numbers of PDDIs (P < 0.001), as illustrated in Table 2.
For all PIMs, the recommendations to avoid use were classified as strong, and half (50%) of the quality of evidence was classified as high. The most frequently used PIMs were metoclopramide, insulin, antipsychotics, nonsteroidal anti-inflammatories, and benzodiazepines (     antiemetic and gastroprokinetic properties, may have been used to improve the success rate of post-pyloric placement of nasojejunal tubes and increase patient tolerance to enteral nutrition. More than one-third (36.1%) of patients who received PIMs were on catheters. Metoclopramide may also be a simple preventive strategy. When catheters are inserted, this agent reduces the risk of aspiration and the incidence of pneumonia. 30,31 Despite the risk of hypoglycemia without improving hyperglycemia management, 25 insulin was prescribed to almost all patients.
A possible explanation for this is the use of glycemic control protocols. Hyperglycemia frequently occurs in critically ill patients and is considered potentially toxic, as it increases the risk of inflammatory and thrombotic events that can contribute to the occurrence of multiple organ and system dysfunction and mortality. 32 The potential benefits of insulin infusion for glycemic control have been demonstrated in studies conducted with critically ill patients, including older people, which have undoubtedly contributed to the prescription of this PIM. 33,34 Explicit criteria such as the Beers criteria facilitate PIM reviews during a patient's hospital journey. They can be recommended to prescribers with an interprofessional approach or incorporated into the clinical decision to guide appropriate prescription, thus reducing unnecessary PIM use. However, these criteria should not replace the clinical judgment of health professionals regarding the patient's condition. Knowledge of these tools can help health teams minimize the dosage and/or duration of PIM to avoid potential adverse drug events in the elderly. 14 In the analysis of drug interactions that should be avoided in older adults, those involving drugs that act on the central nervous system (CNS; opioid analgesics, benzodiazepines, and antipsychotics) are particularly noteworthy. The concomitant use of three or more psychotropic drugs has been verified, a finding corroborated by another study conducted on critically ill patients. 6,7 Almost the entire sample (86.1%) received at least one combination of an object drug and two or more interacting drugs, which increases the risk of falls. 25 The evaluation of the risk and benefit ratio of these combined regimens must be contextualized for critical care situations, especially because a significant portion of the sample was subjected to therapy recommended in guidelines. It can be inferred that the pain, agitation, and delirium triad commonly observed in critically ill patients, although not directly measured, may have been frequent in this sample. 35 Clinical conditions that often overlap require multimodal regimens that include opioid analgesics, benzodiazepines, and other non-benzodiazepine sedatives, which were widely prescribed to older people in this study. A combination of opioid analgesics and benzodiazepines may have been used to enhance the patient's comfort. Opioid analgesics are the first-line agents for treating non-neuropathic pain in critically ill patients, and when combined with benzodiazepines, they can induce deep sedation. 35 Despite evidence indicating that propofol and dexmedetomidine are more acceptable therapeutic options for sedation, 36 benzodiazepines are the main agents used for sedation, which is consistent with previous studies. 37 In teaching hospitals, such as the setting in this study, the longer the length of stay in the ICU, the greater the possibility that different Although it used a convenience sample and had some limitations, the findings of the present study must be interpreted at the epidemiological level. A sample of critically ill older people hospitalized in Brazil´s largest hospital complex, whose clinical staff was responsible for medical education at Latin America's largest university, was analyzed. Although the present study was retrospective, the drugs prescribed, including PIMs, are still used in current therapeutic regimens, especially in multimodal regimens.
The lack of information on the dosage and duration of PIM therapy, therapeutic class duplication, and indications according to clinical conditions may have influenced the estimation of PIM use.
Differences in the profile of PIM use in ICUs were not assessed, an aspect that would definitely reveal particularities according to specialty area. Future studies may overcome these limitations and increase the knowledge of the subject.

CONCLUSION
In summary, the study showed that approximately half (45.8%) of the older adults in the ICUs received a PIM or therapeutic combination that may often be appropriate for the clinical situation.